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The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery

Chronic hepatitis B (CHB) virus infection is the most important cause of HCC and is also associated with tumor progression. The development of viral biomarkers for HCC prognosis is critical in evaluating relative risks to recurrence in the CHB HCC patients. We report that the large HBV surface prote...

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Autores principales: Tsai, Hung-Wen, Lee, Yun-Ping, Yen, Chia-Jui, Cheng, Kuang-Hsiung, Huang, Chien-Jung, Huang, Wenya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140564/
https://www.ncbi.nlm.nih.gov/pubmed/35628188
http://dx.doi.org/10.3390/ijms23105376
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author Tsai, Hung-Wen
Lee, Yun-Ping
Yen, Chia-Jui
Cheng, Kuang-Hsiung
Huang, Chien-Jung
Huang, Wenya
author_facet Tsai, Hung-Wen
Lee, Yun-Ping
Yen, Chia-Jui
Cheng, Kuang-Hsiung
Huang, Chien-Jung
Huang, Wenya
author_sort Tsai, Hung-Wen
collection PubMed
description Chronic hepatitis B (CHB) virus infection is the most important cause of HCC and is also associated with tumor progression. The development of viral biomarkers for HCC prognosis is critical in evaluating relative risks to recurrence in the CHB HCC patients. We report that the large HBV surface protein (LHBS) expression increased in the tumors, implicating that it played a significant role in tumor development. To detect the LHBS in serum and evaluate its association with HCC progression, we developed a sandwich ELISA method for LHBS. The mouse monoclonal antibodies for the pre-S1, pre-S2, and HBS regions were in-house generated and constructed into a chemiluminescent sandwich ELISA system, which allowed sensitive and quantitative measurement of the protein. Using this ELISA assay, we estimated the expression of LHBS in CHB and HCC patients. We found that the serum LHBS level was correlated with the HBS but not the viral titer in serum, indicating that HBV surface proteins’ expression does not mainly depend on viral replication. Moreover, both serum LHBS and HBS levels were lower in the HCC patients than in the CHB. The liver LHBS signals, detected by immunohistochemical staining, showed significant correlations with the serum LHBS and HBS levels. In addition, the more elevated serum LHBS but not HBS level was significantly associated with cirrhosis and worse disease-free and overall survival rates, based on the multivariate analysis. Conclusion: LHBS plays a specific role in tumor progression and is an independent parameter associated with HCC recurrence. Serum LHBS represents a novel noninvasive biomarker for HCC patients with a worse prognosis after surgery.
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spelling pubmed-91405642022-05-28 The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery Tsai, Hung-Wen Lee, Yun-Ping Yen, Chia-Jui Cheng, Kuang-Hsiung Huang, Chien-Jung Huang, Wenya Int J Mol Sci Article Chronic hepatitis B (CHB) virus infection is the most important cause of HCC and is also associated with tumor progression. The development of viral biomarkers for HCC prognosis is critical in evaluating relative risks to recurrence in the CHB HCC patients. We report that the large HBV surface protein (LHBS) expression increased in the tumors, implicating that it played a significant role in tumor development. To detect the LHBS in serum and evaluate its association with HCC progression, we developed a sandwich ELISA method for LHBS. The mouse monoclonal antibodies for the pre-S1, pre-S2, and HBS regions were in-house generated and constructed into a chemiluminescent sandwich ELISA system, which allowed sensitive and quantitative measurement of the protein. Using this ELISA assay, we estimated the expression of LHBS in CHB and HCC patients. We found that the serum LHBS level was correlated with the HBS but not the viral titer in serum, indicating that HBV surface proteins’ expression does not mainly depend on viral replication. Moreover, both serum LHBS and HBS levels were lower in the HCC patients than in the CHB. The liver LHBS signals, detected by immunohistochemical staining, showed significant correlations with the serum LHBS and HBS levels. In addition, the more elevated serum LHBS but not HBS level was significantly associated with cirrhosis and worse disease-free and overall survival rates, based on the multivariate analysis. Conclusion: LHBS plays a specific role in tumor progression and is an independent parameter associated with HCC recurrence. Serum LHBS represents a novel noninvasive biomarker for HCC patients with a worse prognosis after surgery. MDPI 2022-05-11 /pmc/articles/PMC9140564/ /pubmed/35628188 http://dx.doi.org/10.3390/ijms23105376 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsai, Hung-Wen
Lee, Yun-Ping
Yen, Chia-Jui
Cheng, Kuang-Hsiung
Huang, Chien-Jung
Huang, Wenya
The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery
title The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery
title_full The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery
title_fullStr The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery
title_full_unstemmed The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery
title_short The Serum Hepatitis B Virus Large Surface Protein as High-Risk Recurrence Biomarker for Hepatoma after Curative Surgery
title_sort serum hepatitis b virus large surface protein as high-risk recurrence biomarker for hepatoma after curative surgery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140564/
https://www.ncbi.nlm.nih.gov/pubmed/35628188
http://dx.doi.org/10.3390/ijms23105376
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